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Basic Characteristics of Mutations
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Mutation Site
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V843F |
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Mutation Site Sentence
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The genome has four novel non-synonymous mutations in V121D; V843F; A889V; and G1691C positions. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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NSP3 |
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Standardized Encoding Gene
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ORF1a
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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COVID-19
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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Bangladesh |
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Literature Information
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PMID
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33797663
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Title
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Novel mutations in NSP-1 and PLPro of SARS-CoV-2 NIB-1 genome mount for effective therapeutics
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Author
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Hossain MU,Bhattacharjee A,Emon MTH,Chowdhury ZM,Ahammad I,Mosaib MG,Moniruzzaman M,Rahman MH,Islam MN,Ahmed I,Amin MR,Rashed A,Das KC,Keya CA,Salimullah M
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Journal
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Journal, genetic engineering & biotechnology
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Journal Info
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2021 Apr 2;19(1):52
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Abstract
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BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), is rapidly acquiring new mutations. Analysis of these mutations is necessary for gaining knowledge regarding different aspects of therapeutic development. Previously, we have reported a Sanger method-based genome sequence of a viral isolate named SARS-CoV-2 NIB-1, circulating in Bangladesh. The genome has four novel non-synonymous mutations in V121D, V843F, A889V, and G1691C positions. RESULTS: Using different computational tools, we have found V121D substitution has the potential to destabilize the non-structural protein-1 (NSP-1). NSP-1 inactivates the type-1 interferon-induced antiviral system. Hence, this mutant could be a basis of attenuated vaccines against SARS-CoV-2. V843F, A889V, and G1691C are all located in nonstructural protein-3 (NSP-3). G1691C can decrease the flexibility of the protein. V843F and A889V might change the binding pattern and efficacy of SARS-CoV-2 papain-like protease (PLPro) inhibitor GRL0617. V843F substitution in PLPro was the most prevalent mutation in the clinical samples. This mutation showed a reduced affinity for interferon-stimulated gene-15 protein (ISG-15) and might have an impact on innate immunity and viral spread. However, V843F+A889V double mutant exhibited the same binding affinity as wild type PLPro. A possible reason behind this phenomenon can be that V843F is a conserved residue of PLPro which damaged the protease structure, but A889V, a less conserved residue, presumably neutralized that damage. CONCLUSIONS: Mutants of NSP-1 could provide attenuated vaccines against coronavirus. Also, these mutations of PLPro might be targeted to develop better anti-SARS therapeutics. We hope our study will help to get better insides during the development of attenuated vaccine and PLPro inhibitors.
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Sequence Data
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MT509958.1
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